Molecular chemical imaging endoscopic imaging systems

ABSTRACT

Medical imaging systems for use in conjunction with an endoscope are described. Generally, the medical imaging system includes an illumination source configured to generate illuminating photons. The illuminating photons are transmitted to one or more filters configured to filter a first plurality of illuminating photons and generate a first plurality of filtered photons comprising a first passband wavelength and a second plurality of filtered photons comprising a second passband wavelength. A sample is then illuminated with the first plurality of filtered photons and the second plurality of filtered photons to generate a first plurality of interacted photons and a second plurality of interacted photons. One or more detectors are configured to detect the first plurality of interacted photons and the second plurality of interacted photons and generate one or more image data sets.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. Non-Provisionalpatent application Ser. No. 15/932,435, filed Dec. 9, 2015, now U.S.Pat. No. 10,779,713, which claims priority to U.S. ProvisionalApplication Ser. No. 62/113,958 filed on Feb. 9, 2015 and priority toU.S. Provisional Application Ser. No. 62/089,777 filed on Dec. 9, 2014,the contents of each of which are incorporated herein by reference intheir entirety.

BACKGROUND

In performing surgery on the human body, it is essential that surgeonsdo not accidentally cut or otherwise harm organs, passages or otheranatomical structures such as the urethra and ureter. The presence ofblood, fat, arteries, veins, intervening tissue such as muscle andfascia and other highly scattering and absorbing media can make itextremely difficult to locate with great accuracy such organs, passagesand anatomical structures in the immediate vicinity of the surgicalsite. Light emitting catheters have been used to detect irregularitiesin a duct, vessel or organ to assist a surgeon in locating anatomicalstructures of interest to permit the proper performance of the surgicalprocedure. However, there exists a need for improved intraoperativeimaging tools which are capable of real-time detection of anatomicalstructures in assisting surgeons performing delicate operations withoutharming tissue surrounding the surgical site.

SUMMARY OF THE DISCLOSURE

The instant disclosure provides medical imaging systems. The medicalimaging systems may be used in conjunction with an endoscope. Generally,the medical imaging system includes an illumination source configured togenerate illuminating photons. The illuminating photons are transmittedto one or more filters configured to filter a first plurality ofilluminating photons and generate a first plurality of filtered photonscomprising a first passband wavelength and a second plurality offiltered photons comprising a second passband wavelength. A sample isthen illuminated with the first plurality of filtered photons and thesecond plurality of filtered photons to generate a first plurality ofinteracted photons and a second plurality of interacted photons. One ormore detectors are configured to detect the first plurality ofinteracted photons and the second plurality of interacted photons andgenerate one or more image data sets.

In another embodiment, the imaging system includes an illuminationsource configured to illuminate a sample and generate interactedphotons. One or more filters are configured to filter one or more of afirst plurality of the interacted photons and transmit a first passbandwavelength and a second plurality of the interacted photons and transmita second passband wavelength. The first and second passband wavelengthsare transmitted to one or more detectors configured to detect the firstpassband wavelength and the second passband wavelength and generate oneor more image data sets.

In yet another embodiment, the imaging system features an illuminationsource configured to illuminate a sample with one or more of a firstplurality of illuminating photons having a first wavelength to generatea first plurality of interacted photons and a second plurality ofilluminating photons having a second wavelength to generate a secondplurality of interacted photons. One or more detectors are configured todetect the first plurality of interacted photons and the secondplurality of interacted photons to generate one or more image data sets.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an endoscope comprising an imaging system having aplurality of conformal filters in a dual polarization configuration,according to an embodiment;

FIG. 1A is an end-on view of the endoscope according to the embodimentin FIG. 1;

FIG. 1B illustrates a patterned conformal filter configuration with aCCD detector, according to an embodiment;

FIG. 2 illustrates an endoscope comprising an imaging system having aplurality of multivariate optical element (MOE) filters, according to anembodiment;

FIG. 2A is an end-on view of the endoscope according to the embodimentin FIG. 2;

FIG. 2B is a cross-sectional view of the distal end of the endoscopeaccording to the embodiment in FIG. 2;

FIG. 3 illustrates an endoscope comprising an imaging system having aconformal filter, according to an embodiment;

FIG. 3A is an end-on view of the endoscope according to the embodimentin FIG. 3;

FIG. 4 illustrates an endoscope comprising an imaging system having aplurality of conformal filters in a dual polarization configuration forsource illumination modulation, according to an embodiment;

FIG. 4A is an end-on view of the endoscope according to the embodimentin FIG. 4;

FIG. 4B is an end-on view of an alternate embodiment of the endoscopeaccording to the embodiment in FIG. 4;

FIG. 5 illustrates an endoscope comprising an imaging system having anacousto-optic filter, according to an embodiment;

FIG. 5A is an end-on view of the endoscope according the embodiment inFIG. 5;

FIG. 6 illustrates an endoscope comprising an imaging system having aMOE filter wheel, according to an embodiment;

FIG. 6A is an end-on view of the endoscope according to the embodimentin FIG. 6;

FIG. 7 illustrates an endoscope comprising an imaging system having apatterned etalon filter arrangements, according to an embodiment; and

DETAILED DESCRIPTION

The present disclosure features intraoperative medical imaging systemswhich can assist surgeons in various medical procedures. The systemsdisclosed herein are suitable for use as stand-alone devices, or may beincorporated into other medical imaging devices such as a roboticplatform. In one embodiment, the systems disclosed herein may be used inconjunction with an endoscope. The medical imaging systems disclosedherein may provide real-time detection of tumors and anatomic structuresduring endoscopic procedures. Generally, the systems disclosed hereinprovide illuminating a biological sample, collecting photons that haveinteracted with the sample, detecting the interacted photons to generatean image data set of the sample, and analyzing the image data set.Interacted photons may comprise one or more of photons absorbed by asample, photons reflected by a sample, photons scattered by a sample,and photons emitted by a sample. In one embodiment, the medical imagingsystem provides multivariate imaging. Multivariate imaging featuresgenerating two or more wavelengths corresponding to a first image dataset (T1) and a second image data set (T2). These first and second imagedata sets may be analyzed using an optical computation. Multivariateimaging creates enhanced image contrast and increased discriminationbetween a target and background. In certain embodiments, the first imagedata set and the second image data set feature hyperspectral image data.In another embodiment, the medical imaging systems feature imaging framerates of >10 Hz (hyper-cubes/second).

The systems disclosed herein may be used on various biological samples,such as tissues, organs, anatomical structures, physiological systems,cells, blood, fat, nerves, muscle and the like. In certain embodiments,the systems may be employed in various areas of the body, which would beapparent to one of skill in the art in view of this disclosure. Forexample, the systems might be employed to investigate and/or performsurgery in the gastrointestinal tract. In such an application, thesystems may be employed in any of the esophagus, the stomach, theduodenum, the small intestine, the large intestine/colon, the bile duct,the rectum, the anus and the like. The systems may further be employedon structures of the respiratory tract including, without limitation,the nose, the sinuses and the lower respiratory tract. In otherembodiments, the systems disclosed herein may be used to investigateand/or perform surgery on structures comprising the urinary tract, suchas the bladder, ureter, kidneys and so forth. In yet other embodiments,the systems may be employed on structures comprising the femalereproductive system, such as the cervix, uterus, fallopian tubes and thelike. Further, the systems may be employed in medical proceduresperformed during pregnancy, such as to investigate and/or performmedical procedures on the amnion and fetus. In another embodiment, thesystems described herein may be employed to investigate and/or performsurgery on the structures involving the musculoskeletal system, i.e.,orthopaedics, including the structures of the hand, the knee, the elbow,the shoulder, the spine, including the epidural cavity, bursae, muscles,ligaments, connective tissues and the like.

Further, the systems may be configured to discriminate between two ormore different biological samples. For example, the systems disclosedherein may be configured to discriminate between a ureter andsurrounding tissue and fat. In one embodiment, the systems disclosedherein may be employed to differentiate cancer from normal tissue,determine one or more of a cancer stage, cancer progression and cancergrade. In another embodiment, the systems may be employed duringsurgical procedures to remove cancer tissue or tumors found on thebiological sample. In yet another embodiment, the systems describedherein may be employed to differentiate anatomical structures byidentifying a bodily fluid associated with such anatomic structures.Bodily fluids may include, for example, urine, saliva, sputum, blood,feces, mucus, pus, semen, lymph, wound exudate, mammary fluid, vaginalfluid and the like. Anatomical structures having an associated bodilyfluid would be apparent to those of ordinary skill in the art. Asdisclosed herein, the systems of the present disclosure provideillumination to a biological tissue. It is known that such illuminationmay penetrate a biological sample up to several centimeters, dependingon wavelength and tissue type. Thus, such illumination penetrationpermits the imaging of bodily fluids contained inside an anatomicalstructure. Further, the bodily fluids may be directly imaged where theirpresence resides outside of the anatomical structure or other biologicalsample In another embodiment, the systems disclosed herein may beemployed to identify a ureter by detecting urine in or around theureter.

In another embodiment, the instant systems may be employed with the useof one or more contrasting-enhancing agents. Contrast-enhancing agentsmay include one or more stains or dyes. When only one stain or dye isused, the procedure is referred to as staining. Multiple stainingcomprises the use of more than one stain or dye. As used herein, a“stain” or “dye” is any chemical or biological compound that can bind toa substance in a biological sample, to induce a color. For example, astain or dye can bind to a particular cellular or biochemical structure(e.g., cell membrane, organelles, nucleic acid, protein) to inducecontrasts when viewed using the systems described herein. In someembodiments, the stain or dye can induce a color by emittingelectromagnetic radiation at one or more wavelengths when excited (i.e.,fluoresce).

The one or more stains or dyes can be used, for example, in vivo or exvivo. In some embodiments, the stain or dye is any stain or dye suitablefor use in a living organism/individual that does not kill cells, i.e.,a biological stain. Examples of biological stains include, but are notlimited to, azo dyes, arylmethane dyes, cyanine dyes, thiazine dyes,xanthene dyes (e.g., eosin), natural stains (e.g., alizarin red),steroids, trypan blue, janus green, indocyanine green, alizarin red,propidium iodide, erythrosine, 7-aminotinomycin D, and Nile blue. In oneembodiment, the contrasting-enhancing agent is a fluorescentcontrast-enhancing agent. In one embodiment, the contrast-enhancingagent may include a Flourophor. Suitable Fluorophores include animmuno-fluorescent compound, a basophilic compound, an acidophiliccompound, neutral stains and naturally occurring luminescent molecules.

When one or more stains or dyes are used in conjunction with the systemsand methods described herein, a user (e.g., a surgeon) canintra-operatively identify histology, pathology, morphology, position,chemicals, and chemical reactions in or around the biological sample.For example, some (one or more) biological stains can identify cancerouscells so that the surgeon can resect the tumor. Other biological stainscan also identify living cells (tissue) versus non-living cells. Oncethe contrast-enhancing agent is applied to the biological sample, thesample can be irradiated with photons having a wavelength within theillumination wavelength range of the applied contrast-enhancing agent inorder to obtain spectral images as set forth in the instant disclosure.

In another embodiment, the contrast-enhancing agent may be ingested by asubject, where the contrast-enhancing agent will appear in a bodilyfluid. In one embodiment, the contrast-enhancing agent may be takenorally, through an IV or through other means as would be apparent to oneof skill in the art in view of this disclosure. Once thecontrast-enhancing agent is ingested, the target biological sample maybe examined by the systems disclosed herein. The systems may beconfigured to detect the contrast-enhancing agent in the bodily fluid toprovide contrast between structures comprising the bodily fluid andsurrounding biological samples, such as surrounding tissue. For example,a patient may orally ingest a solution comprising a contrast-enhancingagent where the contrast-enhancing agent at a certain time thereafterappears in the patient's urine. A endoscopic procedure may be performedon the kidney area of the patient with a system according to the instantdisclosure. The system is configured to detect the contrast-enhancingagent present in the urine located in an ureter to differentiate theureter and other surrounding tissues.

In another embodiment, a biological tissue may be imaged with a systemaccording to the instant disclosure ex vivo. In such an application, thebiological sample may be removed and analyzed outside of the surgicalsite. Traditional staining methods may be applied to the resected tissueto determine one or more biological characteristics of the sample. Exvivo techniques are known in the art and would be apparent to one ofskill in the art in view of this disclosure.

In another embodiment, the biological sample may be enhanced by applyinga digital stain to the sample. Digital stains are applied to an imagedata set by using an algorithm. The use of a digital stain eliminatesthe need to apply a physical and/or chemical stain to the biologicalsample. Digital stains may be applied to any of the image data setsobtained through the systems disclosed herein. One example of theapplication of a digital stain to a Raman data set may be found in U.S.Patent Application Publication Number 2012/0083678, filed as applicationSer. No. 13/200,779 on Sep. 30, 2011 to Drauch et al. and entitledSYSTEM AND METHOD FOR RAMAN CHEMICAL ANALYSIS OF LUNG CANCER WITHDIGITAL STAINING, assigned to ChemImage Corporation, Pittsburgh, Pa.,the entirety of which is incorporated herein by reference.

Not intending to limit the disclosure in any way, the instant disclosureis directed to analyzing a ureter via an endoscope. Other medicalimaging instrumentation and the detection of other types of biologicalsamples is further contemplated by the instant disclosure and would beapparent to those of skill in the art in view of the instant disclosure.

The medical imaging instruments disclosed herein provide real-timemultivariate imaging by generating a multivariate signal using one ormore detectors. The detectors detect the multivariate signal to produceone or more image data sets. Provided herein are two ways to achievethis result. One such method includes illuminating a sample, collectinginteracted photons that have interacted with the sample, and modulatingthe collected signal prior to passing the signal on to a detector. Asecond method includes modulating the illumination source signal priorto interaction with a sample, collecting interacted photons of themodulated signal, and detecting the interacted photons of the signal.Both processes provide a modulated signal to produce a multivariatechemical image in real-time with enhanced contrast to assist surgeonswith delicate medical procedures. The embodiments contained herein canfurther be configured to provide real-time images displayed in stereovision. Such a configuration would be apparent to those of skill in theart in view of this disclosure. Stereo vision further assists a surgeonby providing the depth perception needed in medical procedures employingmedical imaging techniques, such as in endoscopic procedures. Systemsand methods recited herein provide exemplary embodiments of the instantdisclosure and are not intended to limit the disclosure to anyparticular embodiment.

In the following illustrated embodiments, like reference charactersrefer to like parts.

Modulating Collected Optical Signal

The following embodiment features modulating an optical signal after thecollection of photons that have interacted with a sample.

System having conformal filters in a dual polarization arrangement:

Referring now to FIG. 1, a biological sample 100 may be illuminatedand/or excited by an illumination source 103. In one embodiment, theillumination source 103 may comprise a quartz tungsten halogen lightsource. In other embodiments, the illumination source may comprise ametal halide light source, a light emitting diode (LED), a LED arrayhaving a uniform selection of emitters which emit over a constantwavelength range or a plurality of emitters which emit over a diversityof wavelength ranges, a pulsed LED, a pulsed LED array, a laser, apulsed laser, a broadband illumination source and/or the like. Theillumination source 103 generates illuminating photons that are directedfrom the illumination source 103 to the distal end of an endoscope 102through a fiber optic bundle 104. The endoscope 102 is configured todirect interacted photons 101 that have interacted with the biologicalsample 100 to a polarizing beam splitter 107. Two independently tunableconformal filters 105 a, 105 b are situated along distinct orthogonalbeam paths to filter orthogonal polarization components emerging frompolarizing beam splitter 107. Suitable conformal filters for use in theinstant disclosure may include those disclosed in U.S. PatentApplication Publication Number 2013/0176568 to Priore et al., filed Jan.4, 2013, assigned to Chemimage Corporation and entitled CONFORMAL FILTERAND METHOD OF USE THEREOF, the entirety of which is hereby incorporatedby reference.

In this arrangement, the paths of the filtered beams are not parallelthrough the conformal filters 105 a, 105 b, but are directed byappropriate reflectors, i.e., mirrors, 109 a, 109 b to a beam combiner111. In alternate embodiments, the beam combiner may be a polarizingcube or polarizing beam splitter. In another embodiment, the orthogonalcomponents may comprise the same or different multi-passband wavelengthsΣλ₁ and Σλ₂. In the exemplary embodiment, the conformal filter 105 a isconfigured to generate a polarized multi-passband wavelengths Σλ₁ andconformal filter 105 b is configured to generate a polarizedmulti-passband wavelengths Σλ₂. In the exemplary embodiment,multi-passband wavelengths Σλ₁ and Σλ₂ are directed to a detector 115through a lens assembly (not shown). In another embodiment, themulti-passband wavelengths Σλ₁ and Σλ₂ may be combined as they aredirected to the detector 115. In some embodiments, beam paths from thepolarizing beam splitter 107 to the beam combiner 111 may be madesymmetrical to avoid, for example, a need for infinitely-correctedoptics.

The detector 115 as illustrated comprises a CCD detector. However, thepresent disclosure contemplates that the detector 115 may comprise othersuitable detectors including, for example, a complementarymetal-oxide-semiconductor, a (CMOS) detector, an indium gallium arsenide(InGaAs) detector, a platinum silicide (PtSi) detector, an indiumantimonide (“InSb”) detector, a mercury cadmium telluride (“HgCdTe”)detector, or combinations thereof. Still referring to FIG. 1, the twoconformal filters 105 a and 105 b may be tuned in unison to the samemulti-passband wavelengths (Σλ₁=Σλ₂) using an controller 117. In anotherembodiment, the controller 117 may be configured to independently tuneeach multi-passband wavelengths Σλ₁ and Σλ₂ to respectively processorthogonal components of the input. Therefore, by appropriate control,the conformal filters 105 a and 105 b may be tuned to the samemulti-passband wavelengths or to two different multi-passbandwavelengths (Σλ₁≠Σλ₂) at the same time. The controller 117 may beprogrammable or software-implemented to allow a user to selectively tuneeach conformal filter as desired. In the embodiment of FIG. 1, a fastswitching mechanism (not shown) may be provided to switch between thetwo views (or spectral images) corresponding to spectral data collectedby the detector 117 from each of the conformal filters 105 a and 105 b.Alternatively, two such spectral views or images may be combined oroverlaid into a single image to increase contrast or intensity, or forthe purpose of comparison. The exemplary embodiment in FIG. 1 comprisesa single CCD detector 115 to capture the filtered signals received fromthe conformal filters 105 a and 105 b.

FIG. 1B illustrates an alternative embodiment of the instant disclosure.In this embodiment, the beam combiner 111 and mirror 109 a may beremoved and two detectors may be used. The first conformal filter 105 ais configured to filter and transmit first multi-passband wavelengthscorresponding to a T1 state to a first detector 115 a where the firstdetector 115 a detects the first multi-passband wavelengths andgenerates a first image data set (T1). In similar fashion, the secondconformal filter 105 b is configured to filter and transmit secondmulti-passband wavelengths corresponding to a T2 state to a seconddetector 115 b where the second detector 115 b detects the secondmulti-passband wavelengths and generate a second image data set (T2).

U.S. Patent Application Publication Number 2014/0198315 to Treado etal., filed Jan. 15, 2014 assigned to Chemimage Corporation and entitledSYSTEM AND METHOD FOR ASSESSING ANALYTES USING CONFORMAL FILTERS ANDDUAL POLARIZATION discloses the use of conformal filters in a dualpolarization configuration as discussed above. The reference is herebyincorporated by reference in its entirety.

FIG. 1A illustrates an end-on view of the distal end of the endoscope102. The distal end features a lens 119 for collecting interactedphotons 101 and fiber ends 121 of the fiber optic bundle 103 whichilluminate the biological sample 100 to generate the interacted photons101. The detector 115 detects the multi-passband wavelength from theconformal filters 105 a and 105 b and is configured to generate one ormore image data sets. The image data set may comprise a T1 imagecorresponding to the first multi-passband wavelengths Σλ₁ and a T2 imagecorresponding to the second multi-passband wavelengths Σλ₂. In oneembodiment, the image data set comprises a Raman image data set. The oneor more image data sets generated by the detector 115 may be furtheranalyzed as set forth below.

System Having MOE Filter Arrangements

FIG. 2 illustrates another embodiment featuring modulating the collectedoptical signal. In FIG. 2, an illumination source 103 generatesilluminating photons which traverse along a fiber optic bundle 104through an endoscope 102 and terminate at a series of fiber ends 121 onthe distal end of the endoscope 102 (shown in FIG. 2A). The fiber ends121 emit illuminating photons to illuminate a sample 100 to produce aplurality of interacted photons 101. The interacted photons arecollected by a first collection optic 231 and a second collection optic233. The first collection optic 231 collects a first portion of theinteracted photons 101 and passes these photons on to a firstMultivariate Optical Element “MOE” filter 237 which filters the firstportion of the interacted photons 101 to generate a first portion offiltered photons. The first portion of filtered photons is detected by afirst detector 241. Further, the second collection optic 233 collects asecond portion of the interacted photons 101 and passes these photons onto a second MOE filter 238 to generate a second portion of filteredphotons. The second portion of filtered photons is detected by a seconddetector 239. In one embodiment, the first detector 239 and the seconddetector 241 are CCD detectors. In other embodiments, the detectors 239and 241 may comprise other suitable detectors including, for example, acomplementary metal-oxide-semiconductor, a (CMOS) detector, an indiumgallium arsenide (InGaAs) detector, a platinum silicide (PtSi) detector,an indium antimonide (“InSb”) detector, a mercury cadmium telluride(“HgCdTe”) detector, or combinations thereof

In one embodiment, the first MOE filter 237 may be configured togenerate a first filtered passband. In one embodiment, the first MOEfilter 237 is configured to generate a first filtered passbandconsistent with a randomized target or background. In one embodiment,the second MOE filter 238 may be configured to generate a secondfiltered passband consistent with the target or sample 100. Inembodiments where the first MOE filter 231 is configured to generate afirst filtered passband corresponding to a randomized target orbackground, the second MOE filter 238 may be configured to generate asecond filtered passband corresponding to a target or sample. This typeof embodiment permits discrimination of both a target and a background.

MOEs are typically known in the art. An MOE features wide-band, opticalinterference filters encoded with an application-specific regression (orpattern) specific to a target. MOEs provide multivariate opticalcomputing by performing the optical computation based on the pattern ofthe filter. In other words, MOEs are uniquely tuned to the pattern thatneeds to be measured using multivariate analysis on the filter asopposed to capturing multiple measurements at different wavelengths toestimate the full spectrum of a target and processing this informationby applying multivariate statistics to the spectrum. Thus, MOEs increasethroughput and efficiency over conventional filters, which can increasethe speed of analysis. Suitable MOEs would be apparent to those of skillin the art in view of this disclosure.

The first detector 241 is configured to detect the first filteredpassband from the first MOE filter 237 to generate a first image dataset (T1), and the second detector 239 is configured to detect the secondfiltered passband from the second MOE filter 238 to generate a secondimage data set (T2). The first image data set and the second image dataset may be further analyzed, as set forth below.

Modulating Illumination Source Signal

The following embodiments feature modulating the illumination sourcesignal prior to interaction with a sample.

System Having a Conformal Filter Arrangement

FIG. 3 illustrates an illumination source 103 configured to generateilluminating photons which are transmitted through a filter 305. In oneembodiment, the filter 305 comprises a conformal filter, as disclosedherein. In another embodiment, the filter 305 may comprise otherfilters, such as a liquid crystal tunable filter (“LCTF”), or filters aswould be apparent to those of skill in the art in view of thisdisclosure. In one embodiment, the filter 305 may include amulti-conjugate filter. The filter 305 is controlled by a controller(not shown) that is configured to switch the filter configuration topass first multi-passband wavelengths (Σλ₁) and subsequently be switchedto configure the filter to pass a second multi-passband wavelengths(Σλ₂). In one embodiment, the rate at which the controller switchesbetween the two states is on a millisecond order of magnitude. Thefilter 305 transmits each multi-passband wavelengths, Σλ₁ and Σλ₂,through a fiber optic bundle 309 to the distal end of an endoscope 102where each multi- passband wavelengths exits the distal end of theendoscope 102 via fiber ends 321, as shown in FIG. 3A, to illuminate thesample 100 and produce interacted photons 329. The interacted photons329 are collected by a first detector 331 and a second detector 335located on the distal end of the endoscope 102. The detectors 331 and335 of the illustrated embodiment comprise CCD detectors. However, otherdetectors, such as disclosed herein, may be employed. The first detector331 may be configured to detect substantially only the firstmulti-passband wavelengths. In one embodiment, the first detector 331may be timed, i.e., turned off and on, to detect the firstmulti-passband wavelengths concurrent with the filter 305 transmittingthe first multi-passband wavelengths. Likewise, the second detector 335may be configured to detect substantially only the second multi-passbandwavelengths. In one embodiment, the second detector 335 may be timed,i.e., turned off and on, to detect the second multi-passband wavelengthsconcurrent with the filter 305 transmitting the second multi-passbandwavelengths. In another embodiment, the timing sequence of themodulation between the first multi-passband wavelengths and the secondmulti-passband wavelengths and the detection of the first multi-passbandwavelengths and the second multi-passband wavelengths with thecorresponding detector may be controlled by the controller (not shown).The first detector 231 detects the first multi-passband wavelengths andgenerates a first image data set (T1) and the second detector detectsthe second multi-passband wavelengths and generates a second image dataset (T2). In one embodiment, the first image data set and the secondimage data set may be further analyzed as set forth below.

System Having a Conformal Filters in Dual Polarization Arrangement

FIG. 4 illustrates another embodiment of illumination source modulation.In this embodiment, an illumination source 103 generates an opticalsignal that is transmitted through a polarizing beam splitter 405 whichsplits the optical signal into a first polarization signal and a secondpolarization signal. The first polarization signal is transmitted to afirst filter 409, and the second polarization signal is transmitted to asecond filter 411. In one embodiment, the first filter 409 and thesecond filter 411 each comprise conformal filter, as described herein.In another embodiment, the first filter 409 and second filter 411comprise an LCTF. In one embodiment, the first filter 409 and the secondfilter 411 each may comprise a multi-conjugate filter. The first filter409 is configured to filter the first polarization signal and transmit afirst multi-passband wavelengths (Σλ₁), and the second filter 411 isconfigured to filter the second polarization signal and transmit secondmulti-passband wavelengths (Σλ₂). The first multi-passband wavelengthsand the second multi-passband wavelengths are transmitted from theirrespective filters 409, 411 to the distal end of an endoscope 102 via afirst fiber optic bundle 417 and second fiber optic bundle 419. In oneembodiment, the first fiber optic bundle 417 and the second fiber opticbundle 419 comprise a polarization-maintaining fiber optic bundle.

FIG. 4A and FIG. 4B illustrate different embodiments of the distal endof the endoscope 102. The first fiber bundle 417 and a the second fiberbundle 419 traverse through the endoscope 102 to the distal end. Thefirst fiber bundle 417 terminates at first fiber ends 423 and the secondfiber bundle 417 terminates at second fiber ends 425. FIG. 4Aillustrates one exemplary arrangement of the first fiber ends 423 withrespect to the second fiber ends 425. In this embodiment, the firstfiber ends 423 are distributed together on one side of the distal end ofthe endoscope 102 and the second fiber ends 425 are distributed togetheron the other side of the distal end of the endoscope 102. In FIG. 4B,another embodiment is shown where the first fiber ends 423 and thesecond fiber ends 425 alternate around the distal end of the endoscope102. Suitable arrangements of the fiber ends would be apparent to thoseof skill in the art in view of this disclosure. The sample 100 isilluminated from the multi-first passband wavelengths and the secondmulti-passband wavelengths emitting from the first fiber ends 423 andthe second fiber ends 425, respectively, to generate interacted photons435. The interacted photons 435 are detected by a first detector 437 anda second detector 441 disposed on the distal end of the endoscope 102.In the illustrated embodiment, the first detector 437 and the seconddetector 441 are CCD detectors. However, other suitable detectors, suchas those disclosed herein, may be employed and such detectors would beapparent to one of skill in the art in view of this disclosure. In oneembodiment, the first fiber bundle 417 and the second fiber bundle 419comprise polarization maintaining fiber bundles. In such an embodiment,polarizers (not shown) may be disposed in front of the detectors 437 and441, which are arranged for stereovision, and configured todifferentiate between a T1 state and a T2 state on the basis ofpolarization. In one embodiment, the first detector 437 is configured todetect substantially only interacted photons generated from the firstmulti-passband wavelengths, and the second detector 441 is configured todetect substantially only interacted photons generated from the secondmulti-passband wavelengths. As such, the location of the first fiberends 423 and second fiber ends 425 with respect to the first detector437 and the second detector 441 can be arranged to optimize thedetection of the interacted photons corresponding to the firstmulti-passband wavelengths by the first detector 437 and the interactedphotons corresponding to second multi-passband wavelengths by the seconddetector 441. Once the first detector 437 and the second detector 441detect the interacted photons 435, the first detector 437 is configuredto generate a first image data set (T1), and the second detector 441 isconfigured to generate a second image data set (T2). In one embodiment,the first image data set and the second image data set may be furtheranalyzed.

System Having an Acousto-optic Filter Arrangement

FIG. 5 illustrates an embodiment of the instant disclosure employing anacousto-optic tunable filter (AOTF). This embodiment features anillumination source 103 to generate illuminating photons forilluminating a sample 100. A filter 507 is configured to filter photonsemitted from the illumination source 103. In one embodiment, the filter507 comprises an AOTF in which the AOTF transmits a single passbandwavelength. To achieve a >10 fps sampling rate, the AOTF is rapidlyswitched between target vs background passband wavelengths. In anotherembodiment, the filter comprises a conformal filter based on AOTFtechnology in which the AOTF transmits multi-passband wavelengthssimultaneously. To switch between T1 and T2 states, the conformal filterAOTF is switched in series with microsecond switching speeds. In otherembodiments, multiple conformal AOTFs may be employed in which the T1and T2 states are selected simultaneously. In embodiments employingmultiple acousto-optic filters, each filter may be tuned to variouswavelengths where each filter transmits different multi-passbandwavelengths simultaneously.

Acousto-optic filters are known in the art and, generally, operate bypassing a beam of source light through a substrate, typically quartz.The substrate is vibrated by a piezoelectric transducer modulator. An RFfrequency is applied to the modulator, causing the substrate to vibrate.Source light or radiation is passed through the vibrating substrate,which causes the source light passing through the substrate to diffract,thus creating a filter gradient for the source light. The source lightemitted from the acousto-optic filter can be filtered to a desiredpassband wavelength by the RF frequency applied to the piezoelectrictransducer. Details on the operation of an acousto-optic filter aredescribed in more detail in Turner, John F. and Treado, Patrick J.“Near-Infrared Acousto-Optic Tunable Filter Hadamard TransformSpectroscopy” Applied Spectroscopy, 50.2 (1996), 277-284, which ishereby incorporated by reference in its entirety.

The passband wavelength transmitted from the filter 507 is transmittedto the distal end of an endoscope 102 through a fiber optic bundle 515.FIG. 5A illustrates the distal end of the endoscope 102 and features aplurality of fiber ends 519 from the fiber optic bundle 515. The fiberends 519 transmit the passband wavelength from the filter 507 toilluminate the sample 100 to produce interacted photons 521 which aredetected by a first detector 525 and a second detector 529 located onthe distal end of the endoscope 102. In one embodiment, only onedetector is used, i.e., the first detector 525, to detect a plurality ofthe interacted photons 521. In another embodiment, the interactedphotons 521 are detected by both detectors 525 and 529. In anotherembodiment, a plurality of acousto-optic filters are employed andgenerate a first passband wavelength and a second passband wavelength.The first detector 525 may be configured to detect the first passbandwavelength and generate a first image data set (T1), and the seconddetector 529 may be configured to detect the second passband wavelengthand generate a second image data set (T2). In one embodiment, the firstimage data set and the second image data set may be further analyzed asset forth below.

System Having an MOE Filter Wheel Arrangement

FIG. 6 illustrates another embodiment according to the instantdisclosure. An illumination source 103 generates illuminating photonswhich are transmitted to a filter wheel 605 where the illuminatingphotons are filtered to generate filtered photons. The filter wheel 605comprises a plurality of filter elements 609. In one embodiment, eachfilter element 605 comprises an MOE. Suitable MOEs for use in theinstant disclosure are known in the art and described herein. Eachfilter element 609 may be different and each filter element may beconfigured to filter and transmit a different passband wavelength. Forexample, filter element 609 a may be configured to transmit a wavelengthcorresponding to a background, such as a specific type of tissue oranatomical structure, and filter element 609 b may be configured totransmit a passband wavelength corresponding to an anomaly in a tissuesample, such as a cancerous tumor on the tissue. In this type ofembodiment, the filter wheel 605 can be rotated during a surgicalprocedure to assist a surgeon in distinguishing normal tissue fromcancerous tissue. In another embodiment, the filter elements 609 areconfigured to detect a plurality of different samples. In oneembodiment, the filter elements 609 are configured to discriminatebackground tissue from an anatomical structure such as a ureter.

The filtered photons are transmitted via a fiber optic bundle 603 to thedistal end of the endoscope 102 and exit the distal end of the endoscopethrough a plurality of fiber ends 621 as shown in FIG. 6A. The filteredphotons illuminate the sample 100 and generate a plurality of interactedphotons 601. The interacted photons 601 are detected by a one or moredetectors 619, and the one or more detectors 619 is configured togenerate an image data set (T1). In one embodiment, the image data setmay be further analyzed, as set forth below.

System Having a Patterned Etalon Filter Arrangement

FIG. 7 illustrates another embodiment of the instant disclosure.Illumination source 103 generates illuminating photons which aretransmitted through a fiber optic bundle 104 to the distal end of theendoscope 102 to fiber ends 121. Illuminating photons exit the fiberends 121 and illuminate the sample 100 and generate interacted photons101 from the sample 100. The interacted photons 101 are detected by afirst detector 705 and a second detector 707 disposed on the distal endof the endoscope 102. In one embodiment, the first detector 705 and thesecond detector 707 comprise hyperspectral cameras. In one embodiment,the detectors 705 and 707 comprise a Fabry-Perot interferometric(patterned etalon) filter configuration disposed on each pixel of thedetector. Suitable examples of patterned etalon filter arrangements andassociated detectors are available from Ximea Corporation. The filter oneach pixel is configured to transmit one or more passband wavelengthsfor each pixel. In one embodiment, the first detector 705 comprises apatterned etalon filter arrangement in a mosaic snapshot arrangement. Amosaic snapshot can be acquired over 1088×2048 pixels. In oneembodiment, the mosaic snapshot comprises a 4×4 mosaic having 16wavelength bands. In another embodiment, the mosaic snapshot comprises asnapshot of the sample from 465-630 nm at 11 nm intervals. In anotherembodiment, the mosaic snapshot may comprise a 5×5 mosaic having 25bands over a wavelength range from about 600 to 1,000 nm. The mosaicsnapshot may include a spatial resolution per band of about 512×272 withup to 2 megapixels with interpolation and may collect up to 170data-cubes/sec.

In another embodiment, the first detector 705 and the second detector707 may comprise a patterned etalon filter arrangement for obtaining asnapshot tiled configuration. In one embodiment, the snapshot tiledconfiguration transmits a passband wavelength at each pixel. Thepatterned etalon snapshot tiled filter configuration can acquire up to1088×2048 pixels. In one embodiment, the tiled snapshot has a spectralresolution of up to 32 bands and can detect wavelengths ranging from600-1,000 nm over 12 incremental steps. In another embodiment, thespatial resolution per band is about 256×256. In another embodiment, thetiled snapshot may detect up to 170 data-cubes/sec. The patterned etalonfilter arrangement may also be customized to generate a predeterminedresponse based on the sample to be analyzed and the result desired. Suchcustomization would be apparent to one of skill in the art in view ofthis disclosure.

In one embodiment, the first detector 705 and the second detector 707comprise IMEC mosaic filter arrangements. In such an embodiment, thepatterned etalon mosaic filter arrangements of the first detector 705and the second detector 707 are configured to transmit one or moredifferent wavelength bands at each pixel. In another embodiment, thefirst detector 705 and the second detector 707 comprise patterned etalontiled filter arrangements. In such an embodiment, the patterned etalontiled filter arrangements of the first detector 705 and the seconddetector 707 are configured to detect a different wavelength band ateach pixel. In another embodiment, the second detector is eliminated andthe embodiment employs the first detector 705 having either a snapshotmosaic patterned etalon filter arrangement or a snapshot tiled patternedetalon filter arrangement.

The detectors 705 and 707 are configured to generate one or more imagedata sets for each passband wavelength transmitted from the filterarrangements. In one embodiment, the detectors 705 and 707 areconfigured to generate a first image data set (T1) and a second imagedata set (T2). In one embodiment, the image data sets may be furtheranalyzed, as set forth below.

In yet another embodiment, an illumination source may be configured togenerate illuminating photons at specific wavelengths. For example, theillumination source may comprise a plurality of LEDs where a firstportion of the LEDs are configured to generate a first wavelength and asecond portion of the LEDs are configured to generate a secondwavelength for illuminating a sample. In such an embodiment, a firstdetector may be configured to detect interacted photons from the firstwavelength and generate a first image data set (T1), and a seconddetector may be configured to detect interacted photons from the secondwavelength and generate a second image data set (T2). Other illuminationsources or arrangements may be employed which are capable of producingilluminating photons at a plurality of wavelengths. In one embodiment,the illumination source comprises a modulating laser which is capable ofgenerating multiple wavelengths.

The image data sets described herein may comprise one or more of anultraviolet (UV) image data set, fluorescence image data set, a visible(VIS) image data set, a Raman image data set, a near-infrared (NIR)image data set, a short-wave infrared (SWIR) data set, a mid-infrared(MIR) data set, and a long-wave infrared (LWIR) data set. In anotherembodiment, the image data set comprises a hyperspectral image data set.The image data sets of the instant disclosure may further be analyzed.In one embodiment, the systems disclosed herein may include a fiberarray spectral translator (FAST). Suitable FAST devices are disclosed inU.S. Pat. No. 8,098,373 to Nelson et al., entitled SPATIALLY ANDSPECTRALLY PARALLELIZED FIBER ARRAY SPECTRAL TRANSLATOR SYSTEM ANDMETHOD OF USE, filed Apr. 13, 2010 and assigned to ChemimageCorporation, the disclosure of which is incorporated by reference in itsentirety.

In one embodiment, the systems disclosed herein may comprise a processorand a non-transitory processor-readable storage medium in operablecommunication with the processor. The storage medium may contain one ormore programming instructions that, when executed, cause the processorto analyze the image data sets. In one embodiment, the analysis maycomprise applying an optical computation to the data set. In anotherembodiment, the optical computation may comprise one or more of T1, and(T1−T2)/(T1+T2). Other optical computations known in the art may beapplied. In one embodiment, the analysis may comprise applying one ormore chemometric techniques to the image data sets. The chemometricanalysis may comprise one or more of a multivariate curve resolutionanalysis, a principle component analysis (PCA), a partial least squaresdiscriminant analysis (PLSDA), a k means clustering analysis, a band tentropy analysis, an adaptive subspace detector analysis, a cosinecorrelation analysis, a Euclidian distance analysis, a partial leastsquares regression analysis, a spectral mixture resolution analysis, aspectral angle mapper metric analysis, a spectral information divergencemetric analysis, a Mahalanobis distance metric analysis, and spectralunmixing analysis. In some embodiments, the processor may be configuredto control operation of the system. For example, in embodiments where atunable filter is employed, the process may be configured to cause the acontroller to apply voltages to the tunable filter to obtain the desiredpassband transmission. Further, the processor may be configured tocontrol timing of an illumination source and detectors so that thecorrect detector is in operation for the specific illumination. Otherprocessor configurations are contemplated and would be apparent to oneof skill in the art in view of this disclosure.

The systems according to the instant disclosure may further include adisplay. In some embodiments, the display may include one or moreresults from one or more of the detectors. In another embodiment, thedisplay may include one or more results from the analysis of theprocessor. In one embodiment, the display may include one or moreresults from one or more of the detectors and one or more results fromthe analysis of the processor.

What is claimed is:
 1. An imaging system for use in an endoscope, theimaging system comprising: an illumination source configured to generateilluminating photons; one or more filters selected from conformalfilters, multivariate optical element (MOE) filters, patterned etalonfilters, acousto-optic tunable filters (AOTF), multi-conjugate filtersand combinations thereof, configured to filter a first plurality ofilluminating photons and generate a first plurality of filtered photonscomprising first multi-passband wavelengths and a second plurality offiltered photons comprising second multi-pas sband wavelengths, whereinthe first multi-pas sband wavelengths differ from the secondmulti-passband wavelengths, and wherein a sample is illuminated with thefirst plurality of filtered photons and the second plurality of filteredphotons to generate a first plurality of interacted photons and a secondplurality of interacted photons; at least two detectors comprising afirst detector configured to detect the first plurality of interactedphotons and a second detector configured to detect the second pluralityof interacted photons, the first detector configured to generate a firstimage data set corresponding to the first plurality of interactedphotons and the second detector configured to generate a second imagedata set corresponding to the second plurality of interacted photons. 2.An imaging system for use in an endoscope, the imaging systemcomprising: an illumination source configured to illuminate a sample andgenerate interacted photons; one or more filters selected from conformalfilters, multivariate optical element (MOE) filters, patterned etalonfilters, acousto-optic tunable filters (AOTF), multi-conjugate filters,and combinations thereof, configured to filter one or more of a firstplurality of the interacted photons and transmit first multi-passbandwavelengths and a second plurality of the interacted photons andtransmit second multi-passband wavelengths, wherein the firstmulti-passband wavelengths differ from the second multi-passbandwavelengths; at least two detectors comprising a first detectorconfigured to detect the first multi-passband wavelengths and a seconddetector configured to detect the second multi-passband wavelengths, thefirst detector configured to generate a first image data set of thefirst multi-passband wavelength and the second detector configured togenerate a second image data set of the second multi-passbandwavelength.
 3. The imaging system of claim 1, wherein the illuminationsource includes at least one of a quartz tungsten halogen light source,a metal halide light source, a light emitting diode (LED), a laser, or abroadband illumination source.
 4. The imaging system of claim 3, whereinthe light emitting diode (LED) includes at least one of a LED arrayhaving a uniform selection of emitters which emit over a constantwavelength range, a LED array having a plurality of emitters which emitover a diversity of wavelength ranges, a pulsed LED, or a pulsed LEDarray.
 5. The imaging system of claim 2, wherein the illumination sourceincludes at least one of a quartz tungsten halogen light source, a metalhalide light source, a light emitting diode (LED), a laser, or abroadband illumination source.
 6. The imaging source of claim 5, whereinthe light emitting diode (LED) includes at least one of a LED arrayhaving a uniform selection of emitters which emit over a constantwavelength range, a LED array having a plurality of emitters which emitover a diversity of wavelength ranges, a pulsed LED, or a pulsed LEDarray.